Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 240-354-5 | CAS number: 16230-35-6
Acute Toxicity: dermal
Administrative data
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February 14, 2017 - February 28, 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- fixed dose procedure
- Limit test:
- yes
Test material
- Reference substance name:
- N,N'-(ethoxymethylsilylene)bis[N-methylbenzamide]
- EC Number:
- 240-354-5
- EC Name:
- N,N'-(ethoxymethylsilylene)bis[N-methylbenzamide]
- Cas Number:
- 16230-35-6
- Molecular formula:
- C19H24N2O3Si
- IUPAC Name:
- N,N'-[ethoxy(methyl)silanediyl]bis(N-methylbenzamide)
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature.
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle - France).
- Females nulliparous and non-pregnant: yes.
- Age at study initiation: male animals of the treated group were 7 weeks old and the female were 8 weeks old.
- Weight at study initiation: males= 226.4 ± 4.9, females= 203.2 ± 5.4.
- Fasting period before study: no.
- Housing: during the treatment, the animals were in individual cages. On D1, the animals were put into their cage by 5. The rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains dust free weed shavings which were changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.
- Diet (e.g. ad libitum): foodstuff (ENVIGO 2016) ad libitum.
- Water (e.g. ad libitum): tap-water from public distribution system ad libitum. Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas - Eurofins (France).
- Acclimation period: at least five days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19ºC - 25ºC.
- Humidity (%): 30% - 70% (a relative humidity lower than 30% was registered on 18, 19, 25, 26 and 28 February 2017, the minimum valued measured was 18%).
- Air changes (per hr): at least ten changes cycles per hour.
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (07:00 to 19:00) and telve hours darkness.
IN-LIFE DATES: From: To: 14 February 2017 - 28 February 2017.
Administration / exposure
- Type of coverage:
- other: non-occlusive
- Vehicle:
- water
- Details on dermal exposure:
- TEST SITE
- Area of exposure: dorsal area of the trunk of the animal.
- % coverage: 10% of the body surfade area.
- Type of wrap if used: non-occlusive porous gauze dressing (50x50 mm2 non woven swab, 4-layer patch, MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic micropore TM adhesive tape from 3M).
REMOVAL OF TEST SUBSTANCE
- Washing (if done): after removing the gauze dressings, the treated area was rinsed with destilled water and liquid paraffin.
- Time after start of exposure: 24 h.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.81 mL/kg bw.
- Concentration (if solution): 0.2 g/ml.
- Constant volume or concentration used: yes.
- For solids, paste formed: no.
VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/Kg bw.
- Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5 males and 5 females per dose.
- Control animals:
- yes
- Remarks:
- Study No. TAD-2016-004 (see "Other information on results").
- Details on study design:
- - Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: daily observations, the animals were weighed on day 0 (just before administering the test item) then on day 2, day 7, and day 14.
- Necropsy of survivors performed: yes.
At the end of the study, the animals were euthanized with sodium pentobarbital (Dolethal®). Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. No organ was removed and preserved in view to microscopic examinations.
- Other examinations performed:
Body weight and body weight gain: the animals were weighted on D0 (just before administering the test item) then on D2, D7, and D14.
Clinical signs: Spontaneous activity, Preyer's reflex (noise), Respiratory rate, Convulsions, Tremors, Body temperature, Muscle tone, Palpebral opening, Pupil appearance, Salivation, Lachrymation, Righting reflex, Treatment site, Mortality.
Gross pathology: On D14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels. Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. Parameters examined: Oesophagus, Stomach, Duodenum, Jejunum, Ileon, Caecum, Colon, Rectum, Spleen, Liver, Thymus, Trachea, Lungs, Heart, Kidneys, Urinary Bladder, Ovaries, Uterus, Treatment Area, Adrenals and Pancreas.
Results and discussion
Effect levels
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: erythema was noted in all animals at 48h, but it was fully reversible at day 3
- Mortality:
- No mortality occurred during the study.
- Clinical signs:
- No systemic clinical signs related to the administration of the test item were observed.
Erythema was noted in treated females (5/5) at 48 hours post dose. This reaction was totally reversible at day 3.
Despite this rinse of the treated area (with distilled water and then with liquid paraffin), residual test item was noted on the treated area at 24 and 48 hours post-dose in treated females and at 24 hours post-dose in treated females and at 24 hours post-dose in treated males.
See more details in Tables 1 to 4. - Body weight:
- The body weitght evolution of the animals remained normal throughout the study.
See complete details in Table 5. - Gross pathology:
- The macroscopic examination of the animals at the end of the study did not reveal treatment-realted changes.
See more details in Table 6 and 7.
Any other information on results incl. tables
Table 1. Test item at 2000 mg/kg bw. Observation data sheet.
OBSERVATIONS: |
MALES |
FEMALES |
||||||||
T0 + 1 hours T0 + 3 hours T0 + 5 hours |
Rm 1106 |
Rm 1107 |
Rm 1108 |
Rm 1109 |
Rm 1110 |
Rf 1111 |
Rf 1112 |
Rf 1113 |
Rf 1114 |
Rf 1115 |
Spontaneous activity |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Preyer’s réflex (noise) |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Repiratory rate |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Ringhting reflex |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||||||
N: Normal / None (Convulsions, Tremors)
0: None
Table 2. Test item at 2000 mg/kg bw. Observation data sheet.
OBSERVATIONS: |
MALES |
FEMALES |
||||||||
D1 |
Rm 1106 |
Rm 1107 |
Rm 1108 |
Rm 1109 |
Rm 1110 |
Rf 1111 |
Rf 1112 |
Rf 1113 |
Rf 1114 |
Rf 1115 |
Spontaneous activity |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Preyer’s réflex (noise) |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Repiratory rate |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Ringhting reflex |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Treatment site |
° |
° |
° |
° |
° |
° |
° |
° |
° |
° |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
°: Residue of test item |
°: Residue of test item |
||||||||
N: Normal / None (Convulsions, Tremors)
0: None
Table 3. Test item at 2000 mg/kg bw. Observation data sheet.
OBSERVATIONS: |
MALES |
FEMALES |
||||||||
D2 |
Rm 1106 |
Rm 1107 |
Rm 1108 |
Rm 1109 |
Rm 1110 |
Rf 1111 |
Rf 1112 |
Rf 1113 |
Rf 1114 |
Rf 1115 |
Spontaneous activity |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Preyer’s réflex (noise) |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Repiratory rate |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Ringhting reflex |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Treatment site |
N |
N |
N |
N |
N |
*° |
*° |
*° |
*° |
*° |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
*.erythema °: Residue of test item |
||||||||
N: Normal / None (Convulsions, Tremors)
0: None
Table 4. Test item at 2000 mg/kg bw. Observation data sheet.
OBSERVATIONS: |
MALES |
FEMALES |
||||||||
D3 to d14 |
Rm 1106 |
Rm 1107 |
Rm 1108 |
Rm 1109 |
Rm 1110 |
Rf 1111 |
Rf 1112 |
Rf 1113 |
Rf 1114 |
Rf 1115 |
Spontaneous activity |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Preyer’s réflex (noise) |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Repiratory rate |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Ringhting reflex |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Treatment site |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||||||
N: Normal / None (Convulsions, Tremors)
0: None
Table 5. Test item at 2000 mg/kg bw. Body weight and weight gain in grams.
MALES |
D0 |
D2 |
D2-D0 |
D7 |
D7-D0 |
D14 |
D14-D0 |
||||
Rm 1106 |
230 |
249 |
19 |
287 |
57 |
327 |
97 |
||||
Rm 1107 |
224 |
250 |
26 |
299 |
75 |
353 |
129 |
||||
Rm 1108 |
219 |
251 |
32 |
296 |
77 |
354 |
135 |
||||
Rm 1109 |
231 |
278 |
47 |
317 |
86 |
372 |
141 |
||||
Rm 1110 |
228 |
271 |
43 |
322 |
94 |
354 |
126 |
||||
MEAN |
226.4 |
259.8 |
33.4 |
304.2 |
77.8 |
352.0 |
125.6 |
||||
Standard deviation |
4.9 |
13.7 |
11.6 |
14.8 |
13.9 |
16.1 |
17.0 |
||||
FEMALES |
D0 |
D2 |
D2-D0 |
D7 |
D7-D0 |
D14 |
D14-D0 |
||||
Rf 1111 |
204 |
202 |
-2 |
226 |
22 |
252 |
48 |
||||
Rf1112 |
206 |
221 |
15 |
240 |
34 |
256 |
50 |
||||
Rf 1113 |
210 |
201 |
-9 |
225 |
15 |
240 |
30 |
||||
Rf 1114 |
200 |
221 |
21 |
240 |
40 |
256 |
56 |
||||
Rf 1115 |
196 |
203 |
7 |
224 |
28 |
243 |
47 |
||||
MEAN |
203.2 |
209.6 |
6.4 |
231.0 |
27.8 |
249.4 |
46.2 |
||||
Standard deviation |
5.4 |
10.4 |
12.2 |
8.2 |
9.8 |
7.5 |
9.7 |
||||
Table 6. Necropsy data sheet of males Rm1106 to Rm1110 (28 February 2017)
Found dead:
|
Euthanasia: X
|
At term: X
|
GENERAL APPEARANCE BEFORE AUTOPSY: Normal
|
||
|
Observed Organs
|
Observations
|
* OESOPHAGUS |
X |
N.t.R. |
* STOMACH |
X |
N.t.R. |
* DUODENUM |
X |
N.t.R. |
* JEJUNUM |
X |
N.t.R. |
* ILEON |
X |
N.t.R. |
* CAECUM |
X |
N.t.R. |
* COLON |
X |
N.t.R. |
* RECTUM |
X |
N.t.R. |
* SPLEEN |
X |
N.t.R. |
* LIVER |
X |
N.t.R. |
* THYMUS |
X |
N.t.R. |
* TRACHEA |
X |
N.t.R. |
* LUNGS |
X |
N.t.R. |
* HEART |
X |
N.t.R. |
* KIDNEYS |
X |
N.t.R. |
* URINARY BLADDER |
X |
N.t.R. |
* OVARIES |
X |
N.t.R. |
* UTERUS |
X |
N.t.R. |
* TREATMENT AREA (Skin) |
X |
N.t.R |
* ADRENALS |
X |
N.t.R. |
* PANCREAS |
X |
N.t.R. |
PARTICULARS. None
|
||
N.t.R.: Nothing to report
Table 7. Necropsy data sheet of females Rf1111 to Rm1115 (28 February 2017)
Found dead:
|
Euthanasia: X
|
At term: X
|
GENERAL APPEARANCE BEFORE AUTOPSY: Normal
|
||
|
Observed Organs
|
Observations
|
* OESOPHAGUS |
X |
N.t.R. |
* STOMACH |
X |
N.t.R. |
* DUODENUM |
X |
N.t.R. |
* JEJUNUM |
X |
N.t.R. |
* ILEON |
X |
N.t.R. |
* CAECUM |
X |
N.t.R. |
* COLON |
X |
N.t.R. |
* RECTUM |
X |
N.t.R. |
* SPLEEN |
X |
N.t.R. |
* LIVER |
X |
N.t.R. |
* THYMUS |
X |
N.t.R. |
* TRACHEA |
X |
N.t.R. |
* LUNGS |
X |
N.t.R. |
* HEART |
X |
N.t.R. |
* KIDNEYS |
X |
N.t.R. |
* URINARY BLADDER |
X |
N.t.R. |
* OVARIES |
X |
N.t.R. |
* UTERUS |
X |
N.t.R. |
* TREATMENT AREA (Skin) |
X |
N.t.R |
* ADRENALS |
X |
N.t.R. |
* PANCREAS |
X |
N.t.R. |
PARTICULARS. None
|
||
N.t.R.: Nothing to report
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The dermal LD50 of the test item in rats is greater than 2000 mg/kg bw.
- Executive summary:
A limit test was performed to determine the acute dermal toxicity of the test item in rats according to OECD 402 and EU method B.3, following GLP. The test item was applied onto the intact skin of 10 Sprague Dawley rats (5 males, 5 females) at a dose of 2000 mg/kg bw. All animals were observed once daily for 14 days, survival and body weight were monitored. All animals werte examined macroscopically at the end of the study. There were no mortality ans systemic clinical signs related to the administration of the test irem during the study. Erythema was noted in treated females (5/5) at 48 hours post dose and the reaction was reversible at day 3. Residual test item was also noted on the treated area at 24 and 48 hours post-dose in treated females and at 24 hours post-dose in treated males. Normal changes in body weights and none macroscopic findings were found. In conclusion, the test item was found to be non toxic by dermal route, with an LD50 higher than 2000 mg/kg bw in rats.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
